Impact of vancomycin and polymyxin B on the gut microbiota

The gut microbiota plays a pivotal role in influencing host health, through the production of metabolites and other key signalling molecules. While the impact of specific metabolites or taxa on host cells is well-documented, the broader impact of a disrupted microbiota on immune homeostasis is less understood. This is particularly important in the context of the increasing overuse of antibiotics. The aim of this study was to examine how a shift towards a predominantly gram-positive or gram-negative gut microbiota, mediated by oral antibiotic intake, impacts immune homeostasis both locally in gut-draining lymph nodes (MLNs) and systemically in otherwise healthy animals. To achieve this, mice were orally administered Vancomycin or Polymyxin B for 4 weeks, after which metabolites and immune profiles were assessed. We observed significant changes in caecal metabolites including short-chain fatty acids (SCFAs) and succinate, and identified that dendritic cell (DC) numbers were altered in the MLNs and spleen following antibiotic treatment. Notably, non-specific activation of splenocytes ex vivo revealed that mice with perturbed microbiota had significantly elevated production of TNF. This highlights how antibiotic-mediated disruption of the gut microbiota may program the host towards dysregulated immune responses, predisposing to the development of TNF-associated autoimmune or chronic inflammatory disease.